Reviewed, UniProtKB/Swiss-Prot P15531 (NDKA_HUMAN)

Names and origin

Protein names

Nucleoside diphosphate kinase A
Also known as:
     EC 2.7.4.6
     NDP kinase A
     NDK A
     Tumor metastatic process-associated protein
     Metastasis inhibition factor nm23
     nm23-H1
     Granzyme A-activated DNase
     GAAD

Gene names

Name:	NME1
Synonyms:	NDPKA, NM23

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein existence

Evidence at protein level.

General annotation (Comments)

Function	Major role in the synthesis of nucleoside triphosphates other than ATP.
Catalytic activity	ATP + nucleoside diphosphate = ADP + nucleoside triphosphate.
Cofactor	Magnesium.
Subunit structure	Hexamer of two different chains: A and B (A6, A5B, A4B2, A3B3, A2B4, AB5, B6). Interacts with SET and PRUNE.
Subcellular location	Cytoplasm. Nucleus.
Tissue specificity	Expressed in lung carcinoma cell lines but not in normal lung tissues.
Post-translational modification	The N-terminus is blocked.
Involvement in disease	This protein is found in reduced amount in tumor cells of high metastatic potential. Somatic mutations of NME1 are found in neuroblastoma. Increased NME1 in neuroblastoma is correlated with features of the disease that are associated with aggressive tumors. May therefore have distinct if not opposite roles in different tumors.
Sequence similarities	Belongs to the NDK family.

Ontologies

Keywords
Biological process	Cell cycle Nucleotide metabolism
Cellular component	Cytoplasm Nucleus
Disease	Disease mutation
Ligand	ATP-binding Magnesium Metal-binding Nucleotide-binding
Molecular function	Anti-oncogene Kinase Transferase
PTM	Phosphoprotein
Technical term	3D-structure Direct protein sequencing
Gene Ontology (GO)
Biological process	negative regulation of cell proliferation Ref.5 Traceable author statement. Source: UniProtKB positive regulation of DNA binding Inferred from direct assay. Source: UniProtKB positive regulation of epithelial cell proliferation Inferred from mutant phenotype. Source: HGNC regulation of apoptosis Traceable author statement. Source: UniProtKB
Cellular component	cytoplasm Traceable author statement. Source: UniProtKB nucleus Traceable author statement. Source: UniProtKB
Molecular function	ATP binding Ref.12 Inferred from direct assay. Source: UniProtKB DNA binding Inferred by curator. Source: UniProtKB GTP binding Ref.12 Inferred from direct assay. Source: UniProtKB deoxyribonuclease activity Inferred from direct assay. Source: UniProtKB magnesium ion binding Inferred from direct assay. Source: UniProtKB nucleoside diphosphate kinase activity Ref.12 Inferred from direct assay. Source: UniProtKB protein binding Inferred from physical interaction. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
Ksr1	Q61097	2	EBI-741141,EBI-1536336	From a different organism.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Molecule processing

Chain

1 – 152

152

Nucleoside diphosphate kinase A

Sites

Active site

118

1

Pros-phosphohistidine intermediate

Binding site

12

1

ATP

Binding site

60

1

ATP

Binding site

88

1

ATP

Binding site

94

1

ATP

Binding site

105

1

ATP

Binding site

115

1

ATP

Natural variations

Natural variant

120

1

S → G in neuroblastoma.

Experimental info

Mutagenesis

60

1

F → W: No loss of activity or substrate binding

Mutagenesis

118

1

H → G: Loss of activity

Secondary structure

1

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152

Helix Strand Turn

Details...

Beta strand

6 – 11

6

Helix

13 – 17

5

Helix

21 – 31

11

Beta strand

34 – 41

8

Helix

45 – 51

7

Helix

53 – 55

3

Helix

61 – 69

9

Beta strand

73 – 80

8

Helix

83 – 91

9

Helix

96 – 98

3

Helix

104 – 108

5

Beta strand

117 – 119

3

Helix

123 – 133

11

Helix

136 – 138

3

Helix

147 – 150

4

Sequences

	Sequence		Length	Mass (Da)
	P15531-1 [UniParc]. Last modified April 1, 1990. Version 1. Checksum: AAE9C0DF63CB70A1	FASTA	152	17,149
	10 20 30 40 50 60 MANCERTFIA IKPDGVQRGL VGEIIKRFEQ KGFRLVGLKF MQASEDLLKE HYVDLKDRPF 70 80 90 100 110 120 FAGLVKYMHS GPVVAMVWEG LNVVKTGRVM LGETNPADSK PGTIRGDFCI QVGRNIIHGS 130 140 150 DSVESAEKEI GLWFHPEELV DYTSCAQNWI YE

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Reduced Nm23/Awd protein in tumour metastasis and aberrant Drosophila development." Rosengard A.M., Krutzsch H.C., Shearn A., Biggs J.R., Barker E., Margulies I.M.K., King C.R., Liotta L.A., Steeg P.S. Nature 342:177-180(1989) [PubMed: 2509941] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"Mutation in the nm23 gene is associated with metastasis in colorectal cancer." Wang L., Patel U., Ghosh L., Chen H.C., Banerjee S. Cancer Res. 53:717-720(1993) [PubMed: 7916650] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]	"Isolation and characterization of the human genomic locus coding for the putative metastasis control gene nm23-H1." Dooley S., Seib T., Engel M., Theisinger B., Janz H., Piontek K., Zang K.D., Welter C. Hum. Genet. 93:63-66(1994) [PubMed: 8270257] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[4]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Brain and Lung.
[5]	"Nucleoside diphosphate kinase from human erythrocytes. Structural characterization of the two polypeptide chains responsible for heterogeneity of the hexameric enzyme." Gilles A.-M., Presecan E., Vonica A., Lascu I. J. Biol. Chem. 266:8784-8789(1991) [PubMed: 1851158] [Abstract] Cited for: PROTEIN SEQUENCE, SUBUNIT, ACTIVE SITE.
[6]	"High levels of p19/nm23 protein in neuroblastoma are associated with advanced stage disease and with N-myc gene amplification." Hailat N., Keim D.R., Melhem R.F., Zhu X.X., Eckerskorn C., Brodeur G.M., Reynolds C.P., Seeger R.C., Lottspeich F., Strahler J.R., Hanash S.J. J. Clin. Invest. 88:341-345(1991) [PubMed: 2056128] [Abstract] Cited for: PROTEIN SEQUENCE OF 7-18; 40-49 AND 89-94, DISEASE.
[7]	Lubec G., Afjehi-Sadat L. Submitted (MAR-2007) to UniProtKB Cited for: PROTEIN SEQUENCE OF 7-18; 57-66 AND 89-105, MASS SPECTROMETRY. Tissue: Brain and Cajal-Retzius cell.
[8]	"Identification of genes (SPON2 and C20orf2) differentially expressed between cancerous and noncancerous lung cells by mRNA differential display." Manda R., Kohno T., Matsuno Y., Takenoshita S., Kuwano H., Yokota J. Genomics 61:5-14(1999) [PubMed: 10512675] [Abstract] Cited for: TISSUE SPECIFICITY.
[9]	"Tumor suppressor NM23-H1 is a granzyme A-activated DNase during CTL-mediated apoptosis, and the nucleosome assembly protein SET is its inhibitor." Fan Z., Beresford P.J., Oh D.Y., Zhang D., Lieberman J. Cell 112:659-672(2003) [PubMed: 12628186] [Abstract] Cited for: INTERACTION WITH SET.
[10]	"Phosphorylation of nm23-H1 by CKI induces its complex formation with h-prune and promotes cell motility." Garzia L., D'Angelo A., Amoresano A., Knauer S.K., Cirulli C., Campanella C., Stauber R.H., Steegborn C., Iolascon A., Zollo M. Oncogene 27:1853-1864(2008) [PubMed: 17906697] [Abstract] Cited for: INTERACTION WITH PRUNE.
[11]	"Crystal structure of human nucleoside diphosphate kinase A, a metastasis suppressor." Min K., Song H.K., Chang C., Kim S.Y., Lee K.J., Suh S.W. Proteins 46:340-342(2002) [PubMed: 11835509] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS).
[12]	"Nucleotide binding to nucleoside diphosphate kinases: X-ray structure of human NDPK-A in complex with ADP and comparison to protein kinases." Chen Y., Gallois-Montbrun S., Schneider B., Veron M., Morera S., Deville-Bonne D., Janin J. J. Mol. Biol. 332:915-926(2003) [PubMed: 12972261] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS), MUTAGENESIS OF PHE-60 AND HIS-118.
[13]	"Nm23-H1 mutation in neuroblastoma." Chang C.L., Zhu X.-X., Thoraval D.H., Ungar D., Rawwas J., Hora N., Strahler J.R., Hanash S.M. Nature 370:335-336(1994) [PubMed: 8047138] [Abstract] Cited for: VARIANT NEUROBLASTOMA GLY-120.

Cross-references

Sequence databases

EMBLGenBankDDBJ

X17620 mRNA. Translation: CAA35621.1. Different initiation.
X73066 mRNA. Translation: CAA51527.1.
X75598 Genomic DNA. Translation: CAA53270.1.
BC000293 mRNA. Translation: AAH00293.1.
BC018994 mRNA. Translation: AAH18994.1.

PIR

A33386.

RefSeq

NP_000260.1.

UniGene

Hs.463456

3D structure databases

PDBMSD

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1JXV	X-ray	2.20	A/B/C/D/E/F	1-152	[»]
1UCN	X-ray	2.00	A/B/C	1-152	[»]
2HVD	X-ray	2.15	A/B/C	1-152	[»]
2HVE	X-ray	2.40	A/B/C	1-152	[»]

ModBase

Search...

Protein-protein interaction databases

IntAct

P15531.

PTM databases

PhosphoSite

P15531.

2-D gel databases

Aarhus/Ghent-2DPAGE

4115. IEF.
5112. IEF.

DOSAC-COBS-2DPAGE

P15531.

OGP

P15531.

PMMA-2DPAGE

P15531.

Genome annotation databases

Ensembl

ENSG00000011052. Homo sapiens. [Contig view]

GeneID

4830.

KEGG

hsa:4830.

Organism-specific databases

HGNC

HGNC:7849. NME1.

HPA

CAB002169.
HPA008467.

MIM

156490. gene.

Orphanet

635. Neuroblastoma.

PharmGKB

PA249.

GenAtlas

Search...

GeneCards

Search...

GeneLynx

Search...

Phylogenomic databases

HOVERGEN

P15531.

Enzyme and pathway databases

Reactome

REACT_1698. Nucleotide metabolism.

Gene expression databases

ArrayExpress

P15531.

CleanEx

HS_NME1.

GermOnline

ENSG00000011052. Homo sapiens.

Family and domain databases

InterPro

IPR001564. Nuc_diP_kinase_core.
[Graphical view]

Gene3D

G3DSA:3.30.70.141. NDK. 1 hit.

PANTHER

PTHR11349. Nuc_diP_kinase_core. 1 hit.

Pfam

PF00334. NDK. 1 hit.
[Graphical view]

PRINTS

PR01243. NUCDPKINASE.

ProDom

PD001018. NDK. 1 hit.
[Graphical view] [Entries sharing at least one domain]

SMART

SM00562. NDK. 1 hit.
[Graphical view]

PROSITE

PS00469. NDP_KINASES. 1 hit.
[Graphical view]

BLOCKS

Search...

Other Resources

DrugBank

DB00441. Gemcitabine.
DB00396. Progesterone.

LinkHub

P15531.

SOURCE

Search...

ProtoNet

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Entry information

Entry name

NDKA_HUMAN

Accession

Primary (citable) accession number: P15531

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 1, 1990
Last sequence update:	April 1, 1990
Last modified:	June 10, 2008
This is version 102 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)